The Cellular Basis Of Electroretinogram (ERG) Signals
The Cellular Basis of Electroretinogram(ERG) SignalsLaura J. Frishman, PhDUniversity of HoustonOctober 19, 2015Cellular origins and mechanisms of generation of thevarious waves of the ERGSherry, 2002Modified from Dowling, 19871
The ERG – a non-invasive tool for assayingretinal function and integrity The ERG can inform us about the functional status ofretinal cells and circuits The ERG is useful for detecting and monitoring theprogression of diseases that affect the retina The ERG can be used to monitor effects of therapeuticinterventionsNon-invasive recording of the ERG inman, monkey, mouse etc.Electrodes: Conductive materials in contact with the corneaExample: Contact lens electrodes and DTL fiber electrodesPupils – fully dilated for full field flash ERGCorneas – covered with moistening/ionic conducting solution Fixation (spot or cross) Responses – repeated trials averaged when signals are small Animals and sometimes young children: generally anesthetized usingdrugs with minimal effects on retinal function 2
ERG Stimulus - The diffuse flash full-field or “Ganzfeld” ERGCurrent LED-basedGanzfeld stimulatorsTraditional white light (xenon flash tube iscommon) within a Ganzfeld globeRodsRetinal cells andcircuitsConesMüllercellsAll arerepresented inthe ERGON and OFF Bipolar CellsAmacrine cellsON and OFFGanglion cells3
Rod- c)PERGSTRPhNRLight-adapted(Photopic)Modified from Dowling, 1987Origins of the ERG waves Intraretinal localization Pharmacological dissection Modeling Site-specific lesions/pathology Targeted mutations New stimulation/analysis techniques4
Animal model for necessarily invasiveexperiments: macaque monkey (primate) retinaand ERG are very similar to those of humansIntraretinal localization: Radial CurrentsGeneration of the a-wave (PIII)Circulating current and resulting a-wave from the rodsA-waveAfter Penn & Hagins, 1972; Pugh et al., 19985
Intraretinal localizationCurrent source density analysis in monkey retina localizinga-waves to photoreceptors, b-waves to bipolar cellsPharmacological dissection: Origins of thedark-adapted ERG: Ragnar Granit, 1933Component processes:Disappearing waves –during ether induction:P1- RPE: cP2- Bipolar cells: bP3- Photoreceptors: aFirst pharmacological dissection of the ERG:order of disappearance of “processes” P1, P2, P3following induction of ether anesthesiaHood & Birch, 19926
Modeling and interpreting – transductioncascade* & the a-waveMouse rod OS photocurrent recording (Field & Rieke, 2002)Lamb & Pugh, 1992; Pugh et al., 1998Hood & Birch, 1990*a-wave generated by outer segment,OS current ?The isolated a-wave, is not identical to OScurrentP3 revealed by removing the b-wave Pharmacologic blockade Anoxia – ischemia – occlusion ofinner retinal circulation cCSNB in human2500 Td sI 5 ms7
A model of the a-wave that includes capacitance ofONLModel includes OScurrents, andlongitudinalresistances and ONLcapacitance seen inthe rat retinal slice(Penn & Hagins, 1970)Robson & Frishman, 2014Other photoreceptor-dependent events:The c-wave and slow P3: Photoreceptor responsedependent [K ]0 changes in subretinal space betweenphotoreceptors and RPE affect RPE cells (TEP c-wave)and Müller cells (slow P3)8
Spatial buffer currents in Müller cells move K from areas of high extracellular to areas of lowextracellular concentrationSlow P3 A corneal negative subcomponent ofsubretinal space[K ]othe C-wave A major photoreceptor-dependentcomponent generated by Müller cellcurrentsSlowPIII The K channel blocker, barium (Ba2 )Na eliminates slow P3K Knocking out Kir4.1channelsin miceeliminates slow P3 (the b-waveremains intact)Kofuji et al (2000)Cl vitreousOther outer retinal eventsWaves in the DC ERG withorigins in the retinal pigmentepithelium (RPE)TEP C-waveFOTL
Review chapters with reference lists for papers on ERG origins: Frishman L.J. (2013) Electrogenesis of the ERG In: Ryan Retina 5th edition, edited by D.R.Hinton, MD. Elsevier Mosby, Chapter 7, pp 177-2013. Frishman L.J. (2011) ERG in man, monkey and mouse. Adler’s Physiology of the Eye, 11th edition, edited by Kaufman & Alm.
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